Search Results (1,627)

Autoimmune diseases are chronic inflammatory conditions characterized by the breakdown of immune tolerance to self-antigens. While genetic and environmental factors play key roles, growing evidence highlights chronic stress as a significant contributor to immune dysregulation through its impact on the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis, primarily via cortisol secretion, serves as the major neuroendocrine mediator of stress responses, influencing both immune regulation and systemic homeostasis. This review synthesizes current literature on HPA axis physiology, the mechanisms of cortisol signaling, and the maladaptive effects of chronic stress. Emphasis is placed on clinical and experimental findings linking HPA dysfunction to immune imbalance and autoimmunity, as well as organ-specific consequences across neuroimmune, endocrine, cardiovascular, gastrointestinal, integumentary, and musculoskeletal systems. Chronic stress leads to impaired HPA axis feedback, glucocorticoid receptor resistance, and paradoxical cortisol dysregulation, fostering a pro-inflammatory state. This dysregulation promotes cytokine imbalance, weakens protective immune mechanisms, and shifts the immune response toward autoimmunity. Evidence from both human and animal studies associates persistent HPA dysfunction with diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. HPA axis dysregulation under chronic stress constitutes a critical mechanistic link between psychological stress and autoimmune disease. Understanding these pathways provides opportunities for therapeutic interventions, including stress management, lifestyle modification, and neuroendocrine-targeted treatments. Future research should focus on multi-omics and longitudinal approaches to clarify the reversibility of HPA alterations and identify resilience factors. Full article

Background: Critical illness-related corticosteroid insufficiency (CIRCI) diagnosis remains controversial, largely due to the complex pathophysiology of sepsis, which challenges the reliability of conventional biochemical testing. Recent international guidelines have moved away from strict cortisol threshold-based diagnostic criteria for adrenal insufficiency, relying more on clinical evaluation. However, the applicability and diagnostic accuracy of these revised approaches in non-Western populations remain unexplored. Objective: This study aimed to assessthe diagnostic accuracy and clinical utility of baseline total cortisol levels for guiding corticosteroid therapy in a cohort of patients admitted to the intensive care unit (ICU) with septic shock in a tertiary care hospital in the United Arab Emirates. Methods: A ten-year retrospective observational study (2012–2022) of intensive care patients with septic shock was conducted. CIRCI was operationally defined by a documented clinical decision to administer hydrocortisone >24 h. Receiver Operating Characteristic (ROC) analysis assessed diagnostic performance; Decision Curve Analysis (DCA) evaluated clinical utility of performed cortisol levels. Results: Among 43 patients in the ICU with septic shock, 13 (30.2%) received hydrocortisone (CIRCI group). Mean cortisol was found to be paradoxically higher in the CIRCI group (1341.6 ± 1112.5 vs. 976.0 ± 798.7 nmol/L, p = 0.24). ROC analysis demonstrated poor diagnostic performance (AUC 0.61, 95% CI: 0.44–0.78). International guideline cutoff of <276 nmol/L showed 0% sensitivity in identifying CIRCI. Multiple thresholds yielded negative Youden indices, indicating performance of cortisol levels being worse than a random chance. DCA demonstrated zero net benefit for cortisol-guided therapy across all threshold probabilities when compared to clincial practice strategies. Only clinical factors predicted corticosteroid initiation: high vasopressor requirements (OR 3.2, 95% CI: 1.1–9.4, p = 0.03) and persistent shock >48 h (OR 2.8, 95% CI: 1.0–7.9, p = 0.05). Cortisol level had no predictive value (OR 1.0, 95% CI: 0.9–1.0, p = 0.89). Conclusions: In this cohort, baseline total cortisol demonstrated poor diagnostic accuracy and lacked clinical utility for guiding corticosteroid therapy in patients with sepsis. Our findings reinforce the importance of clinical judgement over biochemical testing in identifying patients with septic shock requiring corticosteroid therapy, in line with the recent international guidelines. Full article

Background: The human fetal adrenal gland is a unique endocrine organ with distinct morphology and functional dynamics, which is significantly different from the postnatal adrenal. Its rapid growth and vital steroidogenic role during gestation have positioned it as a key regulator of fetal development and pregnancy maintenance. Objectives: To provide a comprehensive overview of the morphogenesis, function, regulatory mechanisms, and clinical implications of the human fetal adrenal gland, highlighting recent advances in understanding its development and its role in prenatal and postnatal health outcomes. Methods: A systematic review was conducted, including original research articles focused on human fetuses or validated animal models, examining the genetic, molecular, and hormonal mechanisms underlying adrenal development and function. Studies were excluded if they were editorials, case reports, focused on adult adrenal physiology, had small sample sizes, or were non-English publications. Study quality was evaluated using PRISMA guidelines. Results: The fetal adrenal gland develops from both mesodermal and ectodermal origins, forming three primary zones: fetal, transitional, and definitive. Each zone has distinct functions and developmental pathways. The fetal zone, which predominates, is responsible for producing dehydroepiandrosterone sulfate, DHEA-S, which is crucial for placental estrogen synthesis. The adrenal gland undergoes rapid growth and functional maturation, regulated by ACTH, placental CRH, IGF, and the renin–angiotensin system. Disruption of adrenal function is associated with conditions such as preterm birth, adrenal hypoplasia, congenital adrenal hyperplasia, and intrauterine growth restriction. Emerging evidence suggests that fetal adrenal hormones may influence long-term health through fetal programming mechanisms. Conclusions: The fetal adrenal gland plays a critical and multifaceted role in fetal and placental development. This gland influences placental development via steroid precursors (DHEA-S → estrogen synthesis), while also being regulated by placental factors such as the corticotropin-releasing hormone. Understanding its complex structure–function relationships and regulatory networks is essential for predicting and managing prenatal and postnatal pathologies. Future research should focus on elucidating molecular mechanisms, improving diagnostic tools, and exploring long-term outcomes of altered fetal adrenal function. Full article

Introduction: Renal cell carcinoma (RCC) develops metastatic disease in 30–50% of patients during their disease course, with approximately one quarter presenting with metastases at diagnosis. While the lungs, liver, bones, brain, and adrenal glands are the most frequent metastatic sites, duodenal involvement is exceptionally rare. This uncommon presentation poses diagnostic and therapeutic challenges, particularly regarding the role of surgical resection in the metastatic setting. Objective: We aim to evaluate the clinical presentation, management strategies, and outcomes of patients with duodenal metastasis from RCC, with particular emphasis on the potential role of surgery, through a systematic review of the literature. Methods: A comprehensive electronic search of Medline, Embase, and Scopus was conducted according to PRISMA guidelines. The following MeSH terms were applied: Kidney Neoplasms [MeSH] AND Duodenal Neoplasms/metastasis [MeSH]. Eligible studies included original reports or case series describing RCC with duodenal metastasis. Demographic, clinical, surgical, and survival data were extracted and synthesized. Results: Of 89 records identified, 83 underwent full-text review and 51 met inclusion criteria, representing 55 patients. The median age at diagnosis was 64 years, and 80% of primary tumors arose from the right kidney. Nearly all patients (98%) were symptomatic, most commonly with upper gastrointestinal bleeding, anemia, or obstructive features. Pancreaticoduodenectomy was the predominant surgical approach, performed with curative intent in selected cases. Patients undergoing surgery achieved a 5-year overall survival of 70%, compared with 0% among non-operated patients. Conclusions: Duodenal metastasis from RCC remains an uncommon entity, limiting the strength of available evidence. Nevertheless, our findings suggest that surgical management—when feasible and decided within a multidisciplinary framework—can provide meaningful survival benefit and should be considered as a complement to contemporary systemic therapies for metastatic RCC Full article

Limited data exist regarding the size and volume of adrenal glands in puppies; therefore, the present research aims to describe volumetric and traditional measurements of adrenal glands in computed tomography (CT) images of 26 dogs under 1 year of age. Using OsiriX^®MD v9.0.1, the adrenal volume as well as adrenal length, and the height and width of the cranial and caudal poles were documented. The results were compared with groups based on age, weight at the time of examination, and the dogs’ adult size when patients were clinically re-evaluated after more than 12 months of age. The mean adrenal gland volumes were 0.50 cm³ for the left (range 0.08–1.29 cm³) and 0.41 cm³ for the right (range 0.03–1.10 cm³) adrenal gland. The results showed that older puppies had larger adrenal glands, although the difference did not reach statistical significance. The volume of the adrenal glands correlated positively with body weight and the patients’ adult size. The findings highlight the diagnostic potential of CT-based adrenal volumetry and two-dimensional measurements and support their use in refining reference values for young dogs. The strong correlation between adrenal size and body weight emphasizes the importance of weight-adjusted interpretation in clinical settings. Full article

The adrenal glands are central to the stress response in cetaceans, yet their morphological and molecular changes under chronic stress remain poorly described. We investigated adrenal histology and protein composition in stranded common dolphins (Delphinus delphis) to assess whether post-mortem material can provide insights into stress physiology. Adrenal glands from 58 dolphins recovered along the Irish coast during a period of reported nutritional stress in the species were analyzed for adrenal mass, cortex-to-medulla (C:M) ratios, and cortical cell density. Additionally, two archival formalin-fixed, paraffin-embedded (FFPE) tissues were included in a pilot trial to assess the feasibility of protein extraction and mass spectrometry analysis. While adrenal mass did not differ significantly between stress types, chronically stressed dolphins exhibited significantly higher C:M ratios and cortical mass, consistent with cortical hypertrophy. Protein extraction from FFPE tissues was feasible, with the in-gel digestion method yielding more proteins (136) than the filter-aided sample preparation method (22). These findings demonstrate that histological and proteomic approaches can detect stress-related signatures in dolphins and highlight the potential of archival tissues for retrospective biomarker discovery. Full article

Immortalized adrenal, placental and gonadal cell models are often termed steroidogenic based on steroid hormone production and steroidogenic enzymes. Profiling of ‘classic’ steroid metabolites is common; however, downstream untargeted metabolites remain unidentified. This study characterized steroidogenesis in human adrenal H295R and H295A; placental BeWo and JEG-3; mouse Leydig MA-10; and mouse adrenal Y-1 and OS-3 cells. Steroids were determined under basal, stimulated and serum-free conditions using liquid chromatography–mass spectrometry. This study identified distinct differences in mineralocorticoid and glucocorticoid production in the two human adrenal models and between the human and mouse adrenal models; unconventional hydroxylated progesterone steroid metabolites in all models which were most abundant in MA-10 cells; glucocorticoids and abundant classical androgens in MA-10 cells; 11-oxy androgens in H295R, H295A and MA-10 cells; comparable levels of the classical androgens in H295R and MA-10 cells, while 11-oxy androgen were more abundant in H295R and H295A cells; and high pregnenolone and progesterone in placental models with limited hydroxylated progesterone metabolites. Our detailed protocols and comprehensive steroid profiles provide an invaluable guide to researchers for in vitro investigations into steroidogenesis. Full article

Many individuals suffer from sleep disorders associated with chronic pain, neuroendocrine diseases, and primary sleep disorders. Although cervical manual therapy (CMT) is frequently presumed to enhance sleep quality in clinical settings, evidence regarding its effects on sleep remains inconclusive. We aimed to evaluate the therapeutic effect of CMT and clinical patterns, providing novel insights into its applicability for sleep disorders and further mechanism studies. Methods: A comprehensive literature survey was conducted by using 6 databases through February 2025, to identify randomized controlled trials (RCTs) assessing the effect of CMT on sleep quality as clinical outcome, regardless of primary diseases. Results: Among 1220 initial studies, a total of 10 RCTs involving 552 participants were included. All included RCTs assessed sleep quality using patient-reported outcome measures, while only one study utilized objective assessment via polysomnography. Among them, seven RCTs (70.0%) reported significant improvements in sleep quality that were not dependent on alleviating the primary diseases, with notable enhancements in subjective sleep depth and efficiency rather than sleep duration or latency. Sleep benefits were pronounced in primary sleep disorders, such as obstructive sleep apnea and bruxism, and in sleep disturbances secondary to other conditions, with limited effects in fibromyalgia (FM). Conclusions: With the dysregulated hypothalamic–pituitary–adrenal axis and aberrant serotonergic activity in FM, in this review, we formed a hypothesis and explored the potential effects of CMT on sleep-related serotonergic activity and HPA axis regulation. This scoping review underscores the need for further research to clarify the neuroendocrinological mechanisms underlying CMT’s role in sleep modulation and its potential applications in sleep-related disorders. Full article

Personalized psychiatry represents an innovative therapeutic approach that integrates biological, genetic, and clinical data to optimize the treatment of mental disorders. Laboratory diagnostics play a fundamental role in this process by providing precise biomarkers that characterize pathophysiological mechanisms such as neuroinflammatory processes, oxidative stress, dysfunction of the Hypothalamic–Pituitary–Adrenal (HPA) axis, as well as disturbances in neuroplasticity and neurodegeneration. This article discusses the use of advanced analytical techniques, such as immunoenzymatic assays for pro-inflammatory cytokines (Interleukin-1β- IL-1β; Interleukin-6-IL-6; Interleukin-18-IL-18; and Tumor Necrosis Factor- α - TNF-α). It also emphasizes the role of pharmacogenomic diagnostics in the individualization of psychotropic therapy. Interdisciplinary collaboration between laboratory diagnosticians and clinicians supports the potential for multidimensional analysis of biomarker data in a clinical context, which supports precise patient profiling and monitoring of treatment responses. Despite progress, there are limitations, such as the lack of standardization in measurement methods, insufficient biomarker validation, and limited availability of tests in clinical practice. Development prospects include the integration of multi-marker panels, the use of point-of-care diagnostics, and the implementation of artificial intelligence tools for the analysis of multidimensional data. As a result, laboratory diagnostics are becoming an integral element of personalized psychiatry, enabling a better understanding of the neurobiology of mental disorders and the implementation of more effective therapeutic strategies. Full article

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Background: Adrenoleukodystrophy is a rare, inherited X-linked disease related to mutations in the ABCD1 gene. Peroxisomal β-oxidation is impaired, underpinning the tissue accumulation of very long-chain fatty acids (VLCFAs), especially in the central nervous system (i.e., the white matter and axons), adrenal glands, and testes. VLCFA accumulation contributes to oxidative stress, neuroinflammation, and progressive demyelination, leading to severe neurological sequelae. Though gene therapies and drug development are advancing, dietary management may still play a crucial role in modulating lipid metabolism and mitigating disease progression. Methods: A narrative review of studies published up to May 2025 in major scientific databases was conducted, focusing on biochemical and clinical outcomes, including VLCFA plasma modulation and nutritional status. Results: VLCFA restriction alone has shown limited efficacy due to the counteractive effect of endogenous synthesis. “Lorenzo’s Oil” inhibits VLCFA elongation, yet with inconsistent clinical benefits. Novel dietary strategies, such as the “Bambino Diet” and innovative dietary supplements similar to Lorenzo’s Oil, composed of glyceryl trioleate, glyceryl trierucate, and antioxidants, provide promising biochemical effects, such as reducing VLCFA plasma levels and improving lipid profiles. Malnutrition risk is also increased in X-ALD patients, underscoring the need for personalized nutritional interventions. Conclusions: Dietary strategies are one of the pillars of X-ALD management, to be further combined with pharmacological, gene therapies, and hematopoietic stem cell transplantation. Future research should refine emerging therapies, assess long-term effects, and develop personalized nutritional strategies. Full article

Background: Adrenal insufficiency has been recognized as a condition linked to petrified ear. To further explore this issue, we conducted a review of the literature. Methods: The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines after pre-registration. Excerpta Medica, the National Library of Medicine, and Web of Science databases without language restrictions were used. Inclusion criteria comprised adrenal insufficiency and the presence of petrified ear. Data extraction included demographics, clinical and laboratory features, and outcome. Results: Thirty-six reports were identified, encompassing 40 cases: 38 males and 2 females, aged between 22 and 79 years. All cases exhibited bilateral petrified ears, with 18 cases of primary adrenal insufficiency and 20 cases of central insufficiency. The type of adrenal insufficiency was not specified in two cases. Sixteen patients had concurrent endocrine disorders. In primary adrenal insufficiency, petrified ear was typically (N = 13; 72%) detected two or more years after the endocrine diagnosis. In central adrenal insufficiency, auricular calcification was identified either prior to or at the time (N = 17; 85%) of the endocrine diagnosis. Petrified ear was never associated with hearing impairment and never improved with therapy. Conclusions: In adrenal insufficiency, petrified ear is always bilateral, affects adult males, occurs in both primary and central forms of the disease and does not improve on therapy. In primary insufficiency, this feature is mostly observed two years after the endocrine diagnosis, whereas in central cases, it is identified before or concurrently with the endocrine diagnosis. Full article

Endocrine axes are pathways of interactions involved in various aspects of the organism’s functioning, also implicated in deviations from physiological states leading to pathological conditions. The hypothalamic–pituitary–adrenal (HPA) axis releases corticosteroid hormones promoting adaptation to environmental stimuli (acute stress) or inducing altered conditions due to long-term noxious solicitations (chronic stress). The HP–gonadal (HPG) axis regulates reproductive activities by releasing gonadal steroids. These axes have been shown to engage in reciprocal inhibition under certain conditions, particularly when they rise beyond normal ultradian and circadian fluctuations. Based on the literature data, we reconstructed a neuroendocrine network responsible for this type of interaction. Thereafter, we developed a model of the HPA-HPG inhibition based on a series of nonlinear interactions represented by a system of differential equations in the Matlab environment. The quantitative analysis of the system’s behavior revealed the occurrence of bifurcations leading to bistable behavior, allowing us to detect bifurcation parameters. Bifurcation arises as the system’s components increase hypersensitivity and sustained activity in response to activating inputs. This involves transition from a single low-activity attractor to two distinct attractors, with a new high-activity state representing a breakdown of homeostasis. These results provide insights into the potential involvement of the HPA-HPG interaction in neuroendocrine disorders, and the identification of therapeutic targets from bifurcation parameters. Full article

Chromaffin cells are neuroendocrine cells found in the adrenal medulla and paraganglia. They represent enigmatic cell population with origins and properties that have undergone a change in scientific interpretations over the last few decades. Earlier concepts consider that chromaffin cells derive from neuronal progenitors, and their cell fate is similar to neurons that lack the ability to proliferate and maintain renewal of cell population in postnatal life. Growing evidence of postnatal proliferation and response to proliferative stimuli were inconsistent with traditional views and required their reassessment and further research on chromaffin cell regeneration sources. The present review summarizes data on embryonic origin and development and transcriptional control of the adrenal chromaffin cells as well as available information about their postnatal proliferation. The authors also represent their findings in cellular and molecular events associated with the physiological transition from organ growth to self-maintenance of cell populations in intact rats and in experimental dismorphogenesis of the adrenals. The authors familiarize readers with available information about the early development and molecular changes in chromaffin cells in postnatal period and propose their new theories concerning mechanisms of adrenomedullary chromaffin cell regeneration. Further research on induction and management of these mechanisms will allow us to maintain cultured chromaffin cells in vitro, which will obviously make a significant contribution to practical regenerative medicine. Full article

Background and Objectives: Sick-day medication guidance involves patients self-adjusting medications during sick days to prevent adverse events and minimise exacerbation of their disease states. This review aimed to summarise and synthesise all sick-day interventions provided by healthcare professionals (HCPs) for patients with chronic illnesses, including diabetes, cardiovascular disease, chronic kidney disease (CKD), adrenal insufficiency (AI), rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and asthma. Materials and Methods: A search of Embase, Medline, International Pharmaceutical Abstract, Scopus, Google Scholar, and the grey literature was conducted until July 2025. The review followed the methodological framework according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Data were extracted using a modified TIDieR checklist, and the findings were summarised descriptively and presented thematically. Results: The search included 6932 documents, and 97 met the inclusion criteria: 57 published guidelines/education resources and 40 pieces of original research. Seventy-four interventions were identified for diabetes (18), asthma (32), AI (8), CKD (6), AKI prevention (4), COPD (4), and mixed conditions (2). The most common type of intervention was written information (action plans and information sheets), with education mostly provided by multidisciplinary teams. Novel interventions included 24h phone support and an educational mobile application. Participants showed interest in sick-day interventions and HCPs viewed these interventions as effective, important, and easy to provide. However, interventions did not always translate to improved clinical outcomes, with studies reporting mixed outcomes regarding healthcare utilisation. Nonetheless, some interventions showed improved patient knowledge and satisfaction with care. Conclusions: Multiple interventions are available for asthma and diabetes, with fewer targeting CKD or acute kidney injury (AKI) prevention. While demand for these interventions from consumers and HCPs is high, implementation challenges and inconsistent benefits remain. Further primary research is needed to clarify which intervention features are most effective in yielding meaningful clinical outcomes. Full article